Value of a clinical morphology examination in autism

In an effort to delineate more homogeneous autism subgroups for genetic stu dy, we evaluated 133 consecutive individuals referred to the University of Missouri Autism Center. Each index case underwent a diagnostic evaluation, including a clinical morphology examination, laboratory studies, brain MRI, EEG, and collection of historical, medical, and family data. The 71% (94/1 33) who fulfilled DSM-IV and CARS autism diagnostic criteria were included in this study. Six of 94 were diagnosed with a known genetic disorder. Of t he remaining 88 with apparently "idiopathic autism," 58% (51/88) were pheno typically normal, 22% (19/88) were clearly abnormal, and for 20% (18/88) th e clinical morphology examination was equivocal. The percentage of phenotyp ically abnormal individuals is higher than generally thought and disagrees with the perception that children with autism are usually normally formed. The phenotypically abnormal individuals were 10 times more likely to be dia gnosed with a known genetic syndrome (21% vs. 2%) and were more than twice as likely (29% vs. 14%) to have structurally abnormal brain MRIs than the p henotypically normal propositi, Moreover, the male to female ratio correlat ed with the presence of physical anomalies. The total study group had a mal e to female ratio of 4.2:1; the morphologically normal subgroup, defined on the basis of a normal physical examination, had a sex ratio of 7.5:1 and t he normal subgroup, defined on the basis of both a normal physical examinat ion and a structurally normal brain by MRI had a 23:1 sex ratio. For the ph enotypically abnormal subgroup, the sex ratio was 1.7:1, Since differences in sex ratio are presumably a reflection of differences in genetic constitu tion, we postulate that the phenotypically normal subgroup of individuals w ith "idiopathic autism" is genetically different from the phenotypically ab normal individuals and that differences in the sex ratio in different autis m populations is one indicator of a population's genetic heterogeneity. (C) 2000 Wiley-Liss, Inc.